"This study helps underscore the importance of the microbiome in maintaining health and demonstrates that good bacteria play an integral role in immune defenses against disease," says E. Albert Reece, M.D., Ph.D., M.B.A., Vice President for Medical Affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the University of Maryland School of Medicine. "These findings also provide a potential therapeutic model for other diseases that have been linked to changes in the human intestinal microbiota, such as obesity and diabetes."

What is wrong with this? Well, #1 - the 1st sentence implies a bit too much to me that this study is novel in demonstrating that "good" bacteria play a role in immune defense. When of course this has been shown for many many years. But let's let that slide. Not a big deal.

It is the last line that irks me: "These findings also provide a potential therapeutic model for other diseases that have been linked to changes in the human intestinal microbiota, such as obesity and diabetes."

Hmm. Obesity and diabetes in humans have not been shown to be caused by changes in the microbiome. And therefore it is inaccurate to imply that one could take the fecal transplant for C. difficile model (which is what this current work is about) and extended it to obesity and diabetes. You could say he is careful with words here by saying "linked to" not "caused by" but I think the clear implication here is that he is promoting fecal transplants as a therapy for obesity and diabetes. And he should be more careful (especially as Dean of the University of Maryland School of Medicine). I beg of people out there. Please please please. Microbiome studies have enormous potential. In so many areas. But we risk turning microbiome work into the next medical snake oil if we are not careful with our words.

The paper seems pretty fascinating at first glance. Basically they built on the Jeff Gordon germ free mouse model and introduced a defined set of cultured microbes that came from humans. And then they stages a phage attack on the system and monitored the response of the community to the phage attack.

Figure 1 from Reyes et al.

They (of course) also did a control - in this case with heat killed phage. And they compared what happened to the live phage. I love this concept as they are able to control the microbial community and then test dynamics of how specific phage affect that community inside a living host. Very cool.

The evolutionary history of all life forms is usually represented as a vertical tree-like process. In prokaryotes, however, the vertical signal is partly obscured by the massive influence of horizontal gene transfer (HGT). The HGT creates widespread discordance between evolutionary histories of different genes as genomes become mosaics of gene histories. Thus, the Tree of Life (TOL) has been questioned as an appropriate representation of the evolution of prokaryotes. Nevertheless a common hypothesis is that prokaryotic evolution is primarily tree-like, and a routine effort is made to place new isolates in their appropriate location in the TOL. Moreover, it appears desirable to exploit non–tree-like evolutionary processes for the task of microbial classification. In this work, we present a novel technique that builds on the straightforward observation that gene order conservation (‘synteny’) decreases in time as a result of gene mobility. This is particularly true in prokaryotes, mainly due to HGT. Using a ‘synteny index’ (SI) that measures the average synteny between a pair of genomes, we developed the phylogenetic reconstruction tool ‘Phylo SI’. Phylo SI offers several attractive properties such as easy bootstrapping, high sensitivity in cases where phylogenetic signal is weak and computational efficiency. Phylo SI was tested both on simulated data and on two bacterial data sets and compared with two well-established phylogenetic methods. Phylo SI is particularly efficient on short evolutionary distances where synteny footprints remain detectable, whereas the nucleotide substitution signal is too weak for reliable sequence-based phylogenetic reconstruction. The method is publicly available at http://research.haifa.ac.il/ssagi/software/PhyloSI.zip.

And something continued to catch my eye there. It was the use of "gene order conservation" as the data for the phylogenetic analysis. Hmm. I am generally skeptical of most uses of gene order for inferring phylogeny that I have seen. Why? Well, because it seems to me that gene order is less likely to be a useful character than sequences in alignments (which is the standard for inferring phylogeny). Why do I feel this way? Well, for two main reasons:

1) Sequence alignments are robust. They have been used and used and used and shown to be quite powerful and useful (even though they are not perfect). The rich literature on alignments has shown where and when and how they are useful. And where and when and how they are not. And we have powerful, tested methods to use such alignments.

2) Gene order seems less likely to be robust. I am not saying it is not useful. But the literature I have seen suggests to me that gene order is more prone to convergent evolution than sequence. And gene order is more prone to enormous variation in rates and patterns of evolution. And gene order does not actually have a lot of characters to use compared to whole genome alignment based phylogenetics.

Just got this email that I have pasted below. This seems very very strange. Something is amiss here I think but not sure what. Anyone out there know anything about this?

DearYou are invited to join the Publication Integrity and Ethics (herein referred to as PIE) as one of its founding members. PIE, a not-for profit organisation, offers free membershipto all interested individuals. Please join us and become part of this exciting new movement in the world of publishing ethics:http://www.integrity-ethics.com/register/member/(for standard membership)http://www.integrity-ethics.com/register/editor-in-chief/ (for editor-in-chiefmembership)
As a founding member you will play a central role in shaping the organisation; you will benefit from the many and varied facilities the PIE organisation provides in the world of publishing and ethics. This includes its own guidelines and code of conduct for all membership categories, regular updates in the field, newsletters, e-learning with online exercises and access to our sub-committee’s database. The complaint’s section allows members and adherents to raise issues, regarding any possible breach in the code of ethics and integrity in the publishing sector. PIE provides advice and represents members and adherents freely; it aims to deal with complaints in an ethical manner and resolve them promptly.As part of the commitment to being a member-led, UK-wide and world-wide organisation, PIE intends to identify regional leads to promote the society and ensure that it remains diffuse, responsive and reflects the publication integrity and ethics priorities across the UK and with a global outreach. Members are invited to take part in a shaping PIE by directly communicating with the PIE’s council and other members with regards to the many issues related to this field; they may issue specific guidelines which can be communicated with other national and international organisations.
PIE is able to recommend short online courses, online diplomas and advanced diplomas to its members; these are specifically related to the integrity and ethics in publication and research, law and medical ethics, research governance, strong ethical practice and management. The course title, description and link to the course registration are usually posted on the PIE’s website as a service to our members.
Our online member’s and adherent’s directory is a valuable asset and will allow communications and collaborations between authors, editors, publishers, scientists and a variety of academics in shaping and advancing the world of publishing ethics in the service of humanity.We welcome you to being part of the PIE family.Tim ReevesThe Publication Integrity & EthicsCouncilLondon, United Kingdom

Sunday, November 03, 2013

Well, this just leaves a bad taste in my mouth: Oral Bacteria Create a ‘Fingerprint’ in Your Mouth. Basically, the researchers compared microbial diversity in the oral microbiome of people and they looked at how correlated the microbiome was with ethnicity. And they published a PLOS One paper and wrote a press release about it. And there are many lines in the PR and some in the paper I take issue with. These include:

PR: "The most important point of this paper is discovering that ethnicity-specific oral microbial communities may predispose individuals to future disease”.

Uggh. I cannot find anything anywhere that indicates anything about predisposition to disease

PR: “Nature appears to win over nurture in shaping these communities,” Kumar noted, because African Americans and whites had distinct microbial signatures despite sharing environmental exposures to nutrition and lifestyle over several generations.

Double uggh. So - different ethnic groups have different microbes. And since some of the ethnic groups have similar environmental exposures to each other (actually, they do not even test this - they simply assume this) yet do not have similar micro biomes, therefore the cause of the differences in the microbiomes must be genetic differences between the ethnic groups.

Paper: "Our data demonstrates that ethnicity exerts a selection pressure on the oral microbiome, and that this selection pressure is genetic rather than environmental, since the two ethnicities that shared a common food, nutritional and lifestyle heritage (Caucasians and African Americans) demonstrated significant microbial divergence."

Triple uggh. This should not have been allowed in the paper. Their work in no way demonstrates any genetic component to the differences in the microbiome.

This is certainly a case of overselling the microbiome. But it is also a case of just bad science in relation to the "nature vs. nurture" issues.

Over the last few days I have discussed the meeting with many many people and we have come up with a more detailed / revised draft of the whole meeting. I thought I would share that here -- a formal announcement will be coming soon with details on registering and submitting abstracts for short talks and such.

Publish or Perish? The Future of Academic Publishing and Careers (tentative title ...)

February 13-14, 2013

University of California, DavisHosted by the UC Davis IFHA Innovating Communication in Scholarship (ICIS) Project

Day 1: Innovations in Scholarly Publishing

The Changing Nature of the Journal

Beyond Journals and New Forms of Digital Publishing

Peer Review: Assessment and Evolution

Keynote talk by Yochai Benkler (which will also be part of the UC Davis Provost's Forum)

Saturday, November 02, 2013

Well, I post to Twitter a lot of links to stories of possible interest to readers of this blog. If you want to keep up with all of this chatter and discussion from me and others, you should probably hang out on Twitter a bit. But I know that is not for all. So I am going to try to start posting some of the more relevant links here.